SEPSIS BULLETIN 4 January 2019 - Oxford Patient Safety Collaborative
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Here is the latest edition of the Sepsis Bulletin. The bulletin covers the latest information on sepsis and
comes out fortnightly. Next edition is due 18 January 2019. Older editions are available as pdfs on the
Keeping Up To Date library guide (http://libguides.bodleian.ox.ac.uk/Keeping_up_to_date)
Please also pass the bulletin on to other interested people and encourage them to sign up. Anyone can be
added to the mailing list.
To support you further in keeping up to date, we have a current awareness service, KnowledgeShare. You
let us know about the different areas you are interested in (for example lung cancer, leadership,
orthopaedics, infection control, patient safety, etc.) and we send out an email fortnightly with any new
high‐level reports, studies, guidelines which match. This is a free service. For more information see our
guide. To sign up, fill out our form: https://ox.libguides.com/ld.php?content_id=31673730
SEPSIS BULLETIN
4 January 2019
Neonatal, paediatric and maternal sepsis Adult sepsis (cont.)
Effects of prebiotics on sepsis, necrotizing enterocolitis, The 2018 Surviving Sepsis Campaign’s Treatment
mortality, feeding intolerance, time to full enteral Bundle: When Guidelines Outpace the Evidence
feeding, length of hospital stay, and stool frequency in Supporting Their Use
preterm infants: a meta‐analysis.
Spiegel, R. et al
Chi, C. et al
Ann Emerg Med. 2018 Aug 30. pii: S0196‐
European journal of clinical nutrition December 19, 0644(18)30607‐3
2018
Although well intentioned, the current sepsis bundles
Prebiotics are increasingly recognized as an effective and the potential penalties associated with
measure to promote health and prevent adverse health noncompliance lay a heavy weight on ED care absent
outcomes in preterm infants. We aimed to evidence that a net benefit will follow. The proposed
systematically review the randomized controlled trials Surviving Sepsis Campaign abbreviated bundle
(RCTs) in this area. The results showed that the use of heightens the burden by further restricting the time
prebiotics with preterm infants is safe and can decrease allotted for the identification and treatment of
the incidence of sepsis, mortality, length of hospital patients with suspected sepsis, all without any
stay, and time to full enteral feeding but not NEC. evidence of benefit or knowledge of the logistic
consequences or cost. A more thoughtful approach to
both the identification and management of patients
with sepsis is needed, one that engages allSepsis prediction during outbreaks at neonatal stakeholders and experts, including the emergency
intensive care units through body surface screening for medicine clinicians who treat most patients
Gram‐negative bacteria: systematic review and meta‐ hospitalized with sepsis and who will be responsible
analysis. for implementing these recommendations. A better
strategy will identify more meaningful time stamps,
Harder, T. et al
focus less on the exact volume of fluid administered,
BMC research notes, December 22, 2018, Vol.11(1), and concentrate on identifying the subgroup of septic
p.917 patients who will benefit from timely, appropriate care
while limiting the diagnostic noise and logistic burdens
This systematic review focusses on the prognostic that come with oversensitive screening tools.
accuracy of neonatal body surface screening during
outbreaks caused by Gram‐negative bacteria for
prediction of sepsis. In a previous systematic review we
A Comparison of the Quick Sequential (Sepsis‐Related)
reported that only limited evidence of very low quality
Organ Failure Assessment Score and the National Early
exists regarding the predictive value of this screening
Warning Score in Non‐ICU Patients With/Without
under routine conditions. We aimed to investigate
Infection
whether this is different in outbreak settings. Extending
a previously published systematic review, we show Redfern, O.C. et al
here that in contrast to routine settings sensitivity of
Critical Care Medicine: December 2018 ‐ Volume 46 ‐
body surface screening for sepsis prediction is very
Issue 12 ‐ p 1923–1933
high, while specificity is still insufficient. Surface
screening appears to be a useful component of bundles The Sepsis‐3 task force recommended the quick
of interventions used during outbreaks, but the Sequential (Sepsis‐Related) Organ Failure Assessment
evidence base is still limited. score for identifying patients with suspected infection
who are at greater risk of poor outcomes, but many
hospitals already use the National Early Warning Score
Immunologic biomarkers for diagnostic of early‐onset to identify high‐risk patients, irrespective of diagnosis.
neonatal sepsis. We sought to compare the performance of quick
Sequential (Sepsis‐Related) Organ Failure Assessment
Memar, M.Y. et al
and National Early Warning Score in hospitalized, non‐
The journal of maternal‐fetal & neonatal medicine ICU patients with and without an infection. The
January 2019, Vol.32(1), pp.143‐153 National Early Warning Score outperforms the quick
Sequential (Sepsis‐Related) Organ Failure Assessment
Accurate identification of early onset neonatal sepsis score, irrespective of infection status. These findings
(EOS) is challenging. Blood culture has been considered suggest that quick Sequential (Sepsis‐Related) Organ
as a gold standard method but the identification of EOS Failure Assessment should be re‐evaluated as the
is intricate by a high false‐negative results. This review system of choice for identifying non‐ICU patients with
provides an overview of biomarkers as indicators for suspected infection who are at greater risk of poor
the diagnosis of EOS. There is an affluence of studies outcome.
appraising diagnostic indicators in the identification of
EOS. Acute‐phase reactants, cytokines, and cell surface
antigens have been investigated as indicators for EOS,
A Retrospective Review of the Sepsis Definition after
but none of them are presently in routine clinical
Publication of Sepsis‐3.
setting. Despite the promising data for some
immunologic biomarkers, present evidence shows that Braun, Derek
none of them can constantly diagnose 100% of
The American journal of medicine, November 22,
infections. IL‐6 is the most potent marker for evaluation
2018
of EOS prognosis. Procalciton (PCT) and C‐reactive
protein (CRP) are appropriate indicators for the Two and a half years after the introduction of Sepsis‐3,
detection and monitoring of antibiotics therapy. A clinicians continue not to document Sequential Organ
panel of sepsis biomarkers along with presently routine Failure Assessment (SOFA) scores. The purpose of thistests will make easy earlier identification, appropriate review is to determine if the Third International
management, and improved outcome may be more Consensus Definitions for Sepsis and Septic Shock
efficient than single indicator. (Sepsis‐3) were being utilized in defining sepsis in the
clinical setting. There continue to be variations in what
standard is accepted by both commercial payers and
Screening for colonisation with gentamicin‐resistant the Centers for Medicare and Medicaid (CMS) in
Gram‐negative organisms on the neonatal unit: does diagnosing sepsis. Due to Sepsis‐3 criteria not being
positive screening predict sepsis? accepted by CMS or the Infectious Disease Society of
America, along with it not being able to be
Walker, O. et al operationalized for use in the clinical setting, it is
Archives of disease in childhood. Fetal and neonatal recommended to continue utilizing systemic
edition, January 2019, Vol.104(1), pp.F113‐F114 inflammatory response syndrome criteria plus
infection while Sepsis‐3 continues to be evaluated. It
At our tertiary‐level neonatal unit, surface swabs have will also allow for some time to study any effect it may
been taken weekly to screen for gentamicin‐resistant have on patient outcomes. There is also a need for a
GNB. We conducted a retrospective analysis to uniform definition of sepsis.
investigate whether colonisation screening in our unit
is effective at predicting LOS.
Early Post‐Intensive Care Syndrome among Older Adult
Sepsis Survivors Receiving Home Care.
Severe group A streptococcal infections in mothers and
their newborns in London and the South East, 2010– Riegel, B. et al
2016: assessment of risk and audit of public health Journal of the American Geriatrics Society, November
management 30, 2018
Leonard, A. et al New or worsened disabilities in functional, cognitive,
BJOG : an international journal of obstetrics and or mental health following an intensive care unit (ICU)
gynaecology, January 2019, Vol.126(1), pp.44–53. stay are referred to as post‐intensive care syndrome
(PICS). PICS has not been described in older adults
Are public health guidelines being followed in the receiving home care. Our aim was to examine the
management of mothers and their newborns to reduce relationship between length of ICU stay and PICS
the risk of iGAS infection? We describe cases of invasive among older adults receiving home care. We expected
group A Streptococcus (iGAS) in mothers or neonates that patients in the ICU for 3 days or longer would
and assess management according to national demonstrate significantly more disability in all three
guidelines, which recommend administering antibiotics domains on follow‐up than those not in the ICU. A
to both mother and neonate if either develops iGAS secondary aim was to identify patient characteristics
infection within 28 days of birth and investigation of increasing the odds of disability. Older adults receiving
clusters in maternity units. iGAS infection remains a home care who develop sepsis and are in an ICU for 3
potential postpartum risk. Prophylaxis among neonates days or longer, are likely to develop new or worsened
and storage of isolates from maternity cases can be physical disabilities. Whether these disabilities remain
improved. after the early post‐discharge phase requires further
study.
Genetic polymorphisms and sepsis in premature
neonates. Sepsis: developing new alternatives to reduce
Esposito, S. et al neuroinflammation and attenuate brain injury.
PloS one, 2014, Vol.9(7), p.e101248 Meneses G. et al
Identifying single nucleotide polymorphisms (SNPs) in Ann N Y Acad Sci. 2018 Nov 29.
the genes involved in sepsis may help to clarify thepathophysiology of neonatal sepsis. The aim of this Sepsis occurs when a systemic infection induces an
study was to evaluate the relationships between sepsis uncontrolled inflammatory response that results in
in pre‐term neonates and genes potentially involved in generalized organ dysfunction. The exacerbated
the response to invasion by infectious agents. The peripheral inflammation can induce, in turn,
results show that genetic variability seems to play a neuroinflammation which may result in severe
role in sepsis in pre‐term neonates by influencing impairment of the central nervous system (CNS).
susceptibility to and the severity of the disease, as well Indeed, the ensuing blood‐brain barrier disruption
as the risk of having disease due to specific pathogens. associated with sepsis promotes glial activation and
starts a storm of proinflammatory cytokines in the CNS
that leads to brain dysfunction in sepsis survivors.
Earlier and more targeted treatment of neonatal sepsis. Endotoxic shock induced in mice by peripheral
injection of lipopolysaccharides closely resembles the
Özenci, V. et al peripheral and central inflammation observed in
Acta paediatrica (Oslo, Norway : 1992), January 2019, sepsis. In this review, we provide an overview of the
Vol.108(1), pp.169‐170 neuroinflammatory features in sepsis and of recent
progress toward the development of new anti‐
Neonatal sepsis occurs in 1–2 of the 1000 live born neuroinflammatory therapies seeking to reduce
neonates and accounts for 3‐5% of deaths in term and mortality and morbidity in sepsis survivors.
more than 30% in extremely preterm infants. These
mortality rates due to neonatal infections are
unacceptably high. Immediate and targeted antibiotic Autophagy and skeletal muscles in sepsis.
treatment is crucial in order to improve survival in this
vulnerable population. Pilot study. Mofarrahi, M. et al
PloS one, 2012, Vol.7(10), p.e47265
Which biomarkers reveal neonatal sepsis? Mitochondrial injury develops in skeletal muscles
during the course of severe sepsis. Autophagy is a
Wang K. et al protein and organelle recycling pathway which
PLoS One. 2013 Dec 18;8(12):e82700. functions to degrade or recycle unnecessary,
redundant, or inefficient cellular components. No
We address the identification of optimal biomarkers for information is available regarding the degree of sepsis‐
the rapid diagnosis of neonatal sepsis. We employ both induced mitochondrial injury and autophagy in the
canonical correlation analysis (CCA) and sparse support ventilatory and locomotor muscles. This study tests
vector machine (SSVM) classifiers to select the best the hypotheses that the locomotor muscles are more
subset of biomarkers from a large hematological data prone to sepsis‐induced mitochondrial injury,
set collected from infants with suspected sepsis from depressed biogenesis and autophagy induction
Yale‐New Haven Hospital's Neonatal Intensive Care compared with the ventilatory muscles. We conclude
Unit (NICU). CCA is used to select sets of biomarkers of that locomotor muscles are more prone to sepsis‐
increasing size that are most highly correlated with induced mitochondrial injury, decreased biogenesis
infection. The effectiveness of these biomarkers is then and increased autophagy compared with the
validated by constructing a sparse support vector ventilatory muscles and that autophagy in skeletal
machine diagnostic classifier. We find that the muscles during sepsis is regulated in part through the
following set of five biomarkers capture the essential NFκB transcription factor.
diagnostic information (in order of importance): Bands,
Platelets, neutrophil CD64, White Blood Cells, and Segs.
Further, the diagnostic performance of the optimal set Interleukin 38 Protects Against Lethal Sepsis.
of biomarkers is significantly higher than that of
isolated individual biomarkers. These results suggest an Xu, F. et al
enhanced sepsis scoring system for neonatal sepsis that
The Journal of infectious diseases, August 24, 2018,
includes these five biomarkers. We demonstrate the
Vol.218(7), pp.1175‐1184
robustness of our analysis by compInterleukin 38 (IL‐38) is the most recently
characterized cytokine of the interleukin 1 family.
Mupirocin for Staphylococcus aureus Decolonization of
However, its role in sepsis remains unknown. Our
Infants in Neonatal Intensive Care Units.
findings suggest that IL‐38 attenuates sepsis by
Kotloff, K.L.1et al decreasing inflammation and increasing bacterial
clearance, thus providing a novel tool for antisepsis
Pediatrics. 2019 Jan;143(1). pii: e20181565. therapy.
Staphylococcus aureus (SA) is the second leading cause
of late‐onset sepsis among infants in the NICU. Because
colonization of nasal mucosa and/or skin frequently Sepsis‐The "Gift" That Keeps on Giving, Regardless of
precedes invasive infection, decolonization strategies, Age.
such as mupirocin application, have been attempted to
Simpson, S.Q.
prevent clinical infection, but data supporting this
approach in infants are limited. We conducted a phase Critical care medicine, August 2018, Vol.46(8),
2 multicenter, open‐label, randomized trial to assess pp.1378‐1380
the safety and efficacy of intranasal plus topical
There is little doubt that sepsis is an affliction
mupirocin in eradicating SA colonization in critically ill
associated with aging. Editorial
infants. Application of mupirocin to multiple body sites
was safe and efficacious in eradicating SA carriage
among infants in the NICU; however, after 2 to 3
weeks, many infants who remained hospitalized A minimal set of physiomarkers in continuous high
became recolonized. frequency data streams predict adult sepsis onset
earlier
van Wyk, F. et al
Management of Neonates Born at ≥35 0/7 Weeks’
Gestation With Suspected or Proven Early‐Onset International Journal of Medical Informatics,
Bacterial Sepsis 02/2019, Vol.122, C, pp.55‐62
Puopolo, K. et al Sepsis is a life‐threatening condition with high
mortality rates and expensive treatment costs. To
Pediatrics, Dec 2018, Vol.142(6), p.1 improve short‐ and long‐term outcomes, it is critical to
detect at‐risk sepsis patients at an early stage. A
The incidence of neonatal early‐onset sepsis (EOS) has
random forest classifier was trained to discriminate
declined substantially over the last 2 decades, primarily
between sepsis and non‐sepsis patients. The use of
because of the implementation of evidence‐based
machine learning algorithms on continuous streams of
intrapartum antimicrobial therapy. However, EOS
physiological data can allow for early identification of
remains a serious and potentially fatal illness.
at‐risk patients in real‐time with high accuracy.
Laboratory tests alone are neither sensitive nor specific
enough to guide EOS management decisions. Maternal
and infant clinical characteristics can help identify
newborn infants who are at risk and guide the Exploring the Pathways Revealed by International
administration of empirical antibiotic therapy. The Sepsis Benchmarking.
incidence of EOS, the prevalence and implications of Walkey, A.J.
established risk factors, the predictive value of
commonly used laboratory tests, and the uncertainties Critical care medicine, January 2019, Vol.47(1),
in the risk/benefit balance of antibiotic exposures all pp.135‐137
vary significantly with gestational age at birth. Editorial
Sepsis programme successes are responsible for the
Adult sepsis increased detection of bacteraemia.Association of Corticosteroid Treatment With Simmons, M D et al
Outcomes in Adult Patients With Sepsis: A Systematic
The Journal of hospital infection, January 2019,
Review and Meta‐analysis.
Vol.101(1), pp.93‐99
Fang, F. et al
Escherichia coli bacteraemia reduction targets are
JAMA internal medicine, December 21, 2018 challenging but, in West Wales, this was the key
infection surrogate measure set by the local health
Although corticosteroids are widely used for adults
board in 2013, prior to the introduction of a Welsh
with sepsis, both the overall benefit and potential risks
Government target. The initial plateau of cases was
remain unclear. We conducted a systematic review and
not maintained and prompted this review. Success in
meta‐analysis of the efficacy and safety of
one area (sepsis management) conflicts with 'failure' in
corticosteroids in patients with sepsis. The findings
reducing E. coli bacteraemia. It is argued that targets
suggest that administration of corticosteroids is
need to be considered carefully in the light of all
associated with reduced 28‐day mortality compared
available
with placebo use or standard supportive care. More
research is needed to associate personalized medicine
with the corticosteroid treatment to select suitable
Sepsis: Early Recognition and Optimized Treatment.
patients who are more likely to show a benefit.
Kim, H.I. et al
Tuberculosis and respiratory diseases, January 2019
Identification of subclasses of sepsis that showed
Vol.82(1), pp.6‐14
different clinical outcomes and responses to amount of
fluid resuscitation: a latent profile analysis. Sepsis is a life‐threatening condition caused by
infection and represents a substantial global health
Zhang, Z. et al
burden. Recent epidemiological studies showed that
Critical care (London, England), December 18, 2018, sepsis mortality rates have decreased, but that the
Vol.22(1), p.347 incidence has continued to increase. Although a
mortality benefit from early‐goal directed therapy
Sepsis is a heterogeneous disease and identification of
(EGDT) in patients with severe sepsis or septic shock
its subclasses may facilitate and optimize clinical
was reported in 2001, three subsequent multicenter
management. This study aimed to identify subclasses of
randomized studies showed no benefits of EGDT
sepsis and its responses to different amounts of fluid
versus usual care. Nonetheless, the early
resuscitation. The study identified four subphenotypes
administration of antibiotics and intravenous fluids is
of sepsis, which showed different mortality outcomes
considered crucial for the treatment of sepsis. In 2016,
and responses to fluid resuscitation. Prospective trials
new sepsis definitions (Sepsis‐3) were issued, in which
are needed to validate our findings.
organ failure was emphasized and use of the terms
“systemic inflammatory response syndrome” and
“severe sepsis” was discouraged. However, early
Effect of cytomegalovirus reactivation on the time detection of sepsis with timely, appropriate
course of systemic host response biomarkers in interventions increases the likelihood of survival for
previously immunocompetent critically ill patients with patients with sepsis. Also, performance improvement
sepsis: a matched cohort study. programs have been associated with a significant
van de Groep, K. et al increase in compliance with the sepsis bundles and a
reduction in mortality. To improve sepsis management
Critical care (London, England), December 18, 2018, and reduce its burden, in 2017, the World Health
Vol.22(1), p.348 Assembly and World Health Organization adopted a
Cytomegalovirus (CMV) reactivation in previously resolution that urged governments and healthcare
immunocompetent critically ill patients is associated workers to implement appropriate measures to
with increased mortality, which has been hypothesized address sepsis. Sepsis should be considered a medical
to result from virus‐induced immunomodulation.
Therefore, we studied the effects of CMV reactivationon the temporal course of host response biomarkers in emergency, and increasing the level of awareness of
patients with sepsis. CMV reactivation was not sepsis is essential.
independently associated with changes in the temporal
trends of host response biomarkers in comparison with
non‐reactivating patients. Therefore, these markers Low D‐dimer levels in sepsis: Good or bad?
should not be used as surrogate clinical endpoints for
interventional studies evaluating anti‐CMV therapy. Semeraro, F. et al
Thrombosis research, Vol.174, pp.13‐15 December 5,
2018
APRIL and sTACI could be predictors of multiorgan
dysfunction syndrome in sepsis. DIC is a serious complication of sepsis and increases
the risk of death. D‐dimer (DD) is the most used fibrin‐
Lendak, D.F. et al related marker for DIC diagnosis. However, DD levels
depend on both coagulation and fibrinolysis. Patients
Virulence, December 31, 2018, Vol.9(1), pp.946‐953
with severe sepsis and normal DD were shown to have
Although the role of B cells in sepsis immunoregulation the highest mortality. Allegedly, normal DD in sepsis
has become an interesting topic, there is lack of data masks a DIC form with strong fibrinolysis inhibition.
on the role of B cell function regulators in prediction of Letter
multiorgan dysfunction syndrome (MODS). The aim of
this study was to evaluate the prognostic value of A
Proliferation Inducing Ligand (APRIL) and soluble Effects of antiplatelet therapy on the mortality rate of
Transmembrane Activator and CAML Interactor Protein patients with sepsis: A meta‐analysis.
(sTACI), the main B cell function regulators, in
prediction of MODS development within the first 48h Ouyang, Y. et al
after admission to intensive care unit, among septic Journal of critical care, Vol.50, pp.162‐168 December
patients. Elevated level of sTACI could be the alarm for 5, 2018
the increased B cell apoptosis and development of
immune paralysis. Including these biomarkers into Abnormal platelet activation plays an important role in
predictive scores specific for septic patients may the development of sepsis. The effect of antiplatelet
potentially improve their sensitivity and specificity. drugs on the outcome of patients with sepsis remains
Measurement of their concentrations dynamics could unclear. This meta‐analysis aimed to determine the
contribute to better assessment of sepsis evolution and effect of antiplatelet drugs on the prognosis of
timely introduction of immunomodulatory therapy. patients with sepsis. Antiplatelet drugs, particularly
aspirin, could be used to effectively reduce mortality in
patients with sepsis.
Circulating adrenomedullin estimates survival and
reversibility of organ failure in sepsis: the prospective
observational multinational Adrenomedullin and Doppler‐defined pulmonary hypertension in sepsis and
Outcome in Sepsis and Septic Shock‐1 (AdrenOSS‐1) septic shock.
study. Vallabhajosyula, S. et al
Mebazaa, A. et al Journal of critical care, December 8, 2018, Vol.50,
Critical care (London, England), December 21, 2018, pp.201‐206
Vol.22(1), p.354 The association of pulmonary hypertension (PH) in
Adrenomedullin (ADM) regulates vascular tone and patients with sepsis is lesser understood. In patients
endothelial permeability during sepsis. Levels of with sepsis and septic shock, PH is common and is
circulating biologically active ADM (bio‐ADM) show an noted to be associated with higher short and long‐
inverse relationship with blood pressure and a direct term mortality. Further studies are needed to
relationship with vasopressor requirement. In the understand the mechanisms by which PH is associated
present prospective observational multinational with outcomes.Adrenomedullin and Outcome in Sepsis and Septic
Shock 1 (, AdrenOSS‐1) study, we assessed relationships
An electronic warning system helps reduce the time to
between circulating bio‐ADM during the initial
diagnosis of sepsis.
intensive care unit (ICU) stay and short‐term outcome
in order to eventually design a biomarker‐guided Westphal, G. A. et al
randomized controlled trial. AdrenOSS‐1 shows that
early levels and rapid changes in bio‐ADM estimate Revista Brasileira de terapia intensiva, December 13,
short‐term outcome in sepsis and septic shock. These 2018
data are the backbone of the design of the biomarker‐ To describe the improvements of an early warning
guided AdrenOSS‐2 trial. system for the identification of septic patients on the
time to diagnosis, antibiotic delivery, and mortality.
This was an observational cohort study that describes
the successive improvements made over a period of
10 years using an early warning system to detect
sepsis, including systematic active manual surveillance,
electronic alerts via a telephonist, and alerts sent
directly to the mobile devices of nurses. For all
periods, after an alert was triggered, early treatment
was instituted according to the institutional sepsis
guidelines. Electronic systems help reduce the triage‐
to‐diagnosis time and diagnosis‐to‐antibiotic time in
patients with sepsis.
Need further help? The outreach team at the Bodleian Health Care Libraries is here to support the information
needs of all OUH Trust staff.
We’re happy to help you with literature searches, search skills training and advice, keeping you up to date, and
general references enquiries.
Contact us:
01865 221936
hcl‐enquiries@bodleian.ox.ac.uk
www.bodleian.ox.ac.uk/nhs
Register for OpenAthens to access e‐resources:
https://openathens.nice.org.uk/
Bulletin content based partly on CASH (Current Awareness Service for Health) here
To subscribe/unsubscribe from this bulletin please email library@ouh.nhs.uk or reply to this email.
Please see our privacy notice https://libguides.bodleian.ox.ac.uk/Keeping_up_to_date/privacynoticeYou can also read
